The present project focuses on the characterization of the fourth component of human complement (C4) and its relationship t the Major Histocompatibility Complex in man (HLA). The red cell antigens Chido (Cha) and Rodgers (Rga) are distinct antigenic components of C4 and the aim of this research is to identify the specific biochemical immunological and genetic relationship between C4, Cha and Rga. Studies in normal families and in families with intra HLA recombinant children and with children with genetic recombinations between HLA and HLA-linked genetic markers (Glyoxalase I, Factor B) will be used to resolve the genetic inheritance of the structural genes for C4, Cha and Rga and their interrelationship. Biochemical studies of C4, Cha and Rga will be used to evaluate if the HLA-linked genes controlling C4, Cha and Rga have arisen as a result of gene duplication or if some other genetic mechanism is responsible for the expression of these red cell antigens. The red cells of patients homozygous deficient for C4 will be tested to determine whether expression of these antigens is due merely to uptake of C4 by the red cell from the plasma. Purifed C4 otained from C4F and C4S individuals will also be used to raise specific antibodies against these components in rabbits for use in testing the agglutination of human red cells. Studies of serum levels of C4, Cha and Rga in families and random blood donors in combination with the genetic studies will be used to determine the presence or absence of heterozygous deficiency for each of the two postulated genetic loci of C4 (C4F and C4S).